Psychobiology and Psychopharmacology Flashcards
Mood Disorders/Depressed Symptoms
- Depression may be due to decreased levels of 5HT and/or NE. Most involved circuit is the locus coeruleus.
- Bipolar may be due to interactions between NE, DA, 5HT, ACh, GABA, and peptides
Anxiety Disorders/Anxious Symptoms
- Elevated 5HT and NE, and decreased GABA
2. Raphe Nucleus is most involved circuit
Cognitive Disorders
- ADHD: Dysregulation of attention, activity, and impulsivity. Circuits involved include dorsal anterior cingulate cortex, dorsal lateral prefrontal cortex, and orbital frontal cortex.
- Dysregulation involves DA, NE, and other NTs
Dementia Disorders
- Multi-factorial contributors including amyloid plaques and tau, metabolic, and oxygenation issues
Dopamine
- Excitatory NT important in controlling thoughts and emotions, in frontal cortex, mesocortical tract, and are involved in attention, focus, and depression.
- Controls complex movement in the nigrostriatal DA pathway
- Mesolimbic DA to nucleus accumbens involved with pleasurable behaviors; elevated DA here associated with psychosis
- Tuberoinfundibular pathway: prolactin secretion
Norepinephrine
- Located predominantly in the locus coeruleus
- In frontal cortex regulates mood, attention, concentration (alpha-2 receptors)
- In limbic cortex influences emotions and energy; into cerebellum mediates tremors
- In Brainstem affects blood pressure and innervates heart
- Excitatory NT that helps elevate mood, modulate attention and fatigue
- May also contribute to anxiety disorders
5HT receptors
- Located mostly in the raphe nucleus with projections to:
- Frontal Lobe: Affects mood and depression
- Basal Ganglia: Especially 5HT2A, control of movements and obsessions/compulsions
- Limbic Area: Especially 5HT2A and 5HT2C, related to anxiety and panic
- Hypothalamus: 5HT3 receptors related to appetite and sleep (Mirtazipine)
- Spinal Cord: Influence sexual response and gut
- Peripheral: 5HT3 and 5HT4 receptors in the gut regulate appetite as well as GI motility (after a while, receptors down regulate and, nausea goes away)
GABA
Inhibitory NT
Works to sedate and calm
ACh
Plays a role in memory and cognition
Held in balance with dopamine in the substantia nigra
Gutamate
Primary Excitatory NT
CYP 450 1A2
- Inhibited by SSRI fluvoxamine; therefore increases the levels of theophylline.
- Cigarette smoking induces 1A2, increasing the elimination olanzapine; if pt decreases or quits smoking, dose adjustment needed (EXAM LOVES THIS QUESTION).
CYP 2C19
Reduced activity in 20% of Asian persons, ~5% in Caucasians
CYP 2D6
- Inhibited by fluoxetine, paroxetine, and bupropion.
- If switching from TCA to SSRI, it will have elevated blood levels of TCA who depend on 2D6 for metabolism
- Induction of metabolism of hydrocodone, morphine, and tramadol so will affect pain control.
CYP 3A4 Inhibition
- Inhibited by some SSRIs, nefazodone, and grapefruit juice
- Some BZO levels will rise, such as alprazolam when given with fluoxetine
- Inhibited by erythromycin, will therefore affect carbamazepine level. Use zithromax instead
CYP 3A4 Induction
- Carbamazepine, effecting oral contraceptive levels, as well as the level of carbamazepine itself.
- 3A4 induction greatly affects methadone
- Induced by St. John’s Wort
Exogenous estrogen and Lamictal
-Exogenous estrogen in the form of oral contraception induces 1A4, cutting lamotrigine levels by 50%.
Lithium and NSAIDs
Lithium levels increase with inhibition of prostaglandins, so Ibuprofen will effect levels, but ASA, Sulindac, and Tylenol will not.
CATIE
Clinical Antipsychotic Trials in Intervention Effectiveness
- Patients were walking
- Atypicals are still good, but they weren’t the dream med that we thought they would be.
STEP-BD
Treatment Enhancement Program for Bipolar Disorder
Star-D
Sequenced Treatment Alternatives to Relieve Depression
-Still have a lot of residual depression that wasn’t getting treated.
Typical Antipsychotics MOE
D2 blockade in the mesolimbic and mesocortical tract
Typical Antipsychotics SEs
Sedation/wt gain: Histamine blockade
Orthostatic hypotension/drowsiness: Alpha 1 blockade
Increased Prolactin: D2 blockade in the tuberoinfundibular tract
Anti-Cholinergic effects: Muscarinic blockade
EPS: D2 blockade in nigrostriatal tract
Treatments for EPS
Change med
Lower dose
Benztropine (Cogentin)
Typical Antipsychotics Long-term SEs
Permanent effects on movement seen
TD not reversible
Neuroleptic Malignant Syndrome